TABLE 9–6.

Preventive Treatments Studied for Pediatric Migraine Prevention

Treatment	Dose	Side effects	Comments	2019 AAN-AHS Guideline Comment9
Antiepileptics 9
Topiramate	2–3 mg/kg/d; typical dose 100 mg/d; maximum dose 200 mg/d	Paresthesia, anorexia, weight loss, fatigue, cognitive impairment, decreased perspiration Serious side effects: renal stones, depression, teratogenicity, angle closure glaucoma	Lowers potency of oral contraceptive pill, especially when more than 200 mg/d; recommend folic acid supplementation	Probably more likely than placebo to decrease frequency of headache days
Divalproex sodium	15–30 mg/kg/d up to 1000 mg/d	Nausea, weight gain, dizziness, somnolence, tremor, alopecia; monitor for thrombocytopenia, lymphopenia, elevated liver enzymes Serious side effects: pancreatitis, hyperammonemia, hepatotoxicity, teratogenicity	Recommend folic acid supplementation Not recommended for females of child-bearing age due to teratogenicity	Insufficient evidence
Zonisamide109	4–10 mg/kg/d, usual maximum 200 mg/d	Somnolence, anorexia, weight loss, paresthesia, dizziness, fatigue	Sometimes used if topiramate side effects intolerable	Not reviewed (no pediatric trials)
Levetiracetam110	20–40 mg/kg/d divided into twice daily dosing (usual maximum 3000 mg/d)	Somnolence, fatigue, irritability, behavior/mood change		Not reviewed (no pediatric trials)
Antidepressants 9
Amitriptyline	0.25–1 mg/kg/d (at bedtime)	Sedation, dizziness, dry mouth, weight gain; may cause prolonged QTc		Insufficient evidence when used alone; refer to entry for cognitive-behavioral therapy
Antihypertensives 9
Propranolol	20–40 mg 3 times a day	Sedation, hypotension, bradycardia, weight gain; may worsen depression and exercise-induced asthma		Possibly more likely than placebo to cause 50% reduction in headache frequency
Flunarizine111	5–10 mg at bedtime	Sedation, weight gain	Not available in the United States	Insufficient evidence
Cinnarizine	1.5 mg/kg/d for <30 kg; 50 mg/d for >30 kg	Sedation, weight gain	Not available in the United States	Probably more likely than placebo to decrease headache frequency
Nimodipine	10–20 mg 3 times a day	Abdominal discomfort		Insufficient evidence
Antihistamine 9
Cyproheptadine112	0.25–0.5 mg/kg/d, maximum 16 mg given either at bedtime or divided 2 times a day	Sedation, increased appetite, weight gain	Liquid dosing option, can also treat cyclic vomiting and gastrointestinal pain	Not reviewed (no pediatric migraine trials)
Toxin 9
OnabotulinumtoxinA	74 units or 155 units injected per PREEMPT protocol113 every 12 weeks	Injection site pain, weakness, worsened headache		Insufficient evidence
Nutraceuticals 114
Riboflavin	50–400 mg/d either once daily or divided into two doses	Urine discoloration	Limited studies	Not included
Magnesium	Elemental magnesium 9 mg/ kg/d with food (magnesium oxide divided 3 times a day; others used)	Diarrhea	Limited studies, some positive	Not included
Coenzyme Q10	1–3 mg/kg/d in the morning with food	Insomnia, gastrointestinal upset	Limited studies, some positive	Not included
Vitamin D	Studies have used 400 IU/d for children with normal blood level of Vitamin D; 800 IU/d for mild and 5000 IU/d for moderate Vitamin D deficiency	Well tolerated	Limited studies	Not included
Melatonin115	2–3 mg every day at bedtime	Sedation	Limited studies, some positive	Not included
Polyunsaturated fatty acids	Fish oil compound	Nausea	Limited studies	Not included
Devices
Single-pulse transcranial magnetic stimulation80	Twice daily as preventive therapy with additional pulses for headache attacks plus as needed	Mild discomfort	Open-label pilot study led to US Food and Drug Administration (FDA) clearance in adolescents	Not included
Other
Cognitive-behavioral therapy	10 sessions		Multiple barriers to implementation; biofeedback can be integrated with cognitive-behavioral therapy or is sometimes done separately	Cognitive-behavioral therapy plus amitriptyline more likely than headache education plus amitriptyline to decrease frequency
Acupuncture116	Variable	Discomfort, needle phobia	Safe and effective	Not included

AAN = American Academy of Neurology; AHS = American Headache Society.